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In murine mesangial cells E2 treatment prevented the TGF- These data suggest that E2 regulation of USF1 may be an important modulator of metabolic risk factors and complications.Further studies to determine if there are sex differences in USF1 regulation in the diabetic kidney are warranted.Interestingly, the path by which glucose enters the cell may be critical when it comes to stimulating TGF- Uptake of the glucose through GLUT1 on the basolateral membrane and metabolism of the glucose was required to achieve the priming effect.This may be of great importance because agents to block luminal entry of glucose via SGLT2 may soon be used as a means of lowering blood glucose level.In these trials renal disease and its markers were not a primary outcome, limiting the usefulness of these trials for understanding the impact of sex and hormone replacement therapy on renal disease.In addition, although E2 supplementation may be beneficial to women, it is unlikely to serve as an effective treatment strategy for men.Diabetic men already have higher-than-normal levels of E2, and men on E2 therapy experience negative sexual side effects.

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Glucose is taken up into cells via the glucose transporters (GLUTs) on the basolateral side and the sodium/glucose co-transporters (SGLTs) on the luminal side.To date, no large-scale clinical trials have been designed to examine hormone replacement therapy interventions for diabetic renal disease.Estrogen is considered protective against the development and progression of cardiovascular disease as well, and in the 1990s two large studies, the Heart and Estrogen/progestin Replacement Study trial and the Women’s Health Initiative trial, directly examined the role of hormone replacement therapy in the treatment of cardiovascular disease in women.To the best of our knowledge there has not been a direct comparison of macrophage infiltration in the diabetic kidney between males and females.However, in the spontaneously hypertensive rat model of kidney disease males had higher levels of macrophage infiltration of the kidney than females, and OVX in females increased macrophage number.).

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